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Objectives There are concerns for COVID-19 vaccination in causing thyroid dysfunction and triggering thyroid autoimmunity. Also, data on the impact of pre-existing thyroid autoimmunity on COVID-19 vaccination efficacy are limited. We evaluated the impact of COVID-19 vaccination on thyroid function and antibodies, and the influence of pre-existing thyroid autoimmunity on neutralizing antibody (NAb) responses. Methods Adults without history of COVID-19 or thyroid disorders who received COVID-19 vaccination between 14 June 2021 and 8 August 2021 at three vaccination centers were recruited. All participants received two doses of vaccines. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies were measured at baseline and 8 weeks after the first dose of vaccination. Post-vaccination NAb against SARS-CoV-2 receptor-binding domain was measured. Results In total, 215 individuals were included (129 BNT162b2 [60%] and 86 CoronaVac [40%] recipients): mean age 49.6 years, 37.2% men, and 12.1% positive for anti-TPO/anti-Tg at baseline. After vaccination, TSH levels did not change (p=0.225), but fT4 slightly increased (from 12. 0±1.1 to 12.2±1.2 pmol/L, p Conclusion COVID-19 vaccination was associated with a modest increase in anti-thyroid antibody titers. Anti-TPO increase was greater among BNT162b2 recipients. However, there was no clinically significant thyroid dysfunction 8 weeks post-vaccination. NAb responses were not influenced by pre-existing thyroid autoimmunity. Our results provided important reassurance to people to proceed to COVID-19 vaccination. Presentation: No date and time listed

Introduction Circulating thrombospondin-2 (TSP2) has been associated with adverse cardiovascular outcomes in patients with heart failure (HF). Type 2 diabetes (T2D) increases HF risk and induces TSP2 tissue expression. Here, we investigated prospectively the role of circulating TSP2 as a novel biomarker of incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in T2D. Methods Baseline serum TSP2 level was measured in 4949 T2D patients from the Hong Kong West Diabetes Registry to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 level was measured in another 146 T2D patients without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year. Results Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 level was independently associated with the development of HHF (HR 1.31, 95%CI 1.06–1.62, p=0.014) after adjustments for conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level at baseline, as well as use of medications including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, frusemide, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. In the echocardiographic study, baseline serum TSP2 level was independently associated with increase in average E/e' and left atrial volume index (p=0.04 and Conclusion Serum TSP2 level was independently associated with both incident HHF and deterioration in diastolic function in T2D, suggesting its potential to be developed as a novel HF biomarker in T2D. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Background The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM. Methods Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively. Results The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e′ (all P Conclusion Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.

Additional file 1. Table S1. Intraobserver and interobserver reproducibility of echocardiography parameters. Table S2. Clinical characteristics and echocardiography parameters of participants at baseline and follow-up. Table S3. Univariate linear regression showing the variables associated with changes in echocardiography parameters. Table S4. Clinical characteristics of participants stratified by incident MACE.

Sanjuan Nandin et al. describe an innovative approach based on antigen-dependent activation of human memory B cells in culture. It results in the rapid generation of human antibodies against infectious agents and offers the potential for therapeutic antibody production and vaccine development., Vaccines remain the most effective tool to prevent infectious diseases. Here, we introduce an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells in culture. This stimulation induces antigen-specific B cell proliferation, differentiation of B cells into plasma cells, and robust antibody secretion after a few days of culture. We validated this strategy using cells from healthy donors to retrieve human antibodies against tetanus toxoid and influenza hemagglutinin (HA) from H1N1 and newly emergent subtypes such as H5N1 and H7N9. Anti-HA antibodies were cross-reactive against multiple subtypes, and some showed neutralizing activity. Although these antibodies may have arisen as a result of previous influenza infection, we also obtained gp120-reactive antibodies from non–HIV-infected donors, indicating that we can generate antibodies without prior antigenic exposure. Overall, our novel approach can be used to rapidly produce therapeutic antibodies and has the potential to assess the immunogenicity of candidate antigens, which could be exploited in future vaccine development.

Dendritic cells (DC) are required for priming antigen-specific T cells and acquired immunity to many important human pathogens, including Mycobacteriuim tuberculosis (TB) and influenza. However, inappropriate priming of auto-reactive T cells is linked with autoimmune disease. Understanding the molecular mechanisms that regulate the priming and activation of naïve T cells is critical for development of new improved vaccines and understanding the pathogenesis of autoimmune diseases. The serine/threonine kinase IKKα (CHUK) has previously been shown to have anti-inflammatory activity and inhibit innate immunity. Here, we show that IKKα is required in DC for priming antigen-specific T cells and acquired immunity to the human pathogen Listeria monocytogenes. We describe a new role for IKKα in regulation of IRF3 activity and the functional maturation of DC. This presents a unique role for IKKα in dampening inflammation while simultaneously promoting adaptive immunity that could have important implications for the development of new vaccine adjuvants and treatment of autoimmune diseases.

Annual influenza epidemics continue to cause worldwide morbidity, mortality and societal disruption, especially among the aged residents of residential care homes for the elderly (RCHEs). Vaccination remains the most effective measure to prevent influenza and its associated complications. The seasonal influenza vaccine uptake rates among RCHE staff were much lower than that among residents. In order to increase uptake of influenza vaccination among RCHE staff in Hong Kong, this study developed and evaluated a multimodal vaccine promotion program (VPP) based on identified factors affecting vaccination acceptance or refusal within the Hong Kong Chinese context. Vaccine acceptance was found to be significantly associated with belief in vaccine efficacy, duration of service, staff group and providing direct care to residents. The focus group study revealed that RCHE staff's belief in the efficacy and safety of the vaccine played a major role in vaccine acceptance. VPP effectiveness was evaluated with a cluster randomised controlled trial among RCHEs with staff vaccination rates below 50%. Compared with 2008/09, the 2009/10 mean staff vaccination rates increased significantly in both the intervention (39.4% to 59.6% (P < 0.001)) and control groups (36.3% to 47.6% (P = 0.008)). RCHE staff in the intervention group had a higher vaccination rate than in the control group (59.6% versus 47.6%, P = 0.072). This program reinforces the importance of a comprehensive and culturally sensitive approach to promote influenza vaccination for RCHE staff.

International audience; Inflammation is a salutary response to insult or injury that normally resolves with no detriment to the host. While the mechanisms and mediators that regulate the onset of inflammation have been well characterized we still know relatively little about the endogenous mechanisms that terminate the inflammatory response (Lawrence and Gilroy, 2007). Nuclear factor (NF)-kappaB is a generic term for a family of ubiquitous transcription factors with diverse physiological functions (Bonizzi and Karin, 2004; Caamano and Hunter, 2002). NF-kappaB transcription factors are formed by dimerisation of Rel proteins; RelA (p65), c-Rel, RelB, p50, p52. Various hetero or homodimers of Rel proteins can be formed in a tissue and stimulus specific manner, genetic evidence suggests these transcription factors have a critical role in cell survival and pro-inflammatory signalling pathways, which have been extensively reviewed elsewhere (Bonizzi and Karin, 2004; Caamano and Hunter, 2002). The critical role for NF-kappaB in pro-inflammatory gene expression has led to an enormous effort to develop inhibitors of this pathway for the treatment of chronic inflammation (Karin et al., 2004). However, recent research using modern molecular genetic approaches has revealed new anti-inflammatory roles for NF-kappaB that may have important implications for targeting this pathway in the treatment of inflammatory diseases. In this review we will discuss the emerging role of NF-kappaB in the resolution of inflammation and some of the potential mechanisms attributed to this function.